Highly purified thromboplastin (tissue factor) was previously found to activate the complement system in human serum, through interaction with the classical but not the alternative complement pathway. The biochemical characteristics of the reaction between thromboplastin and purified Cl will be investigated. Experiments suggesting that this reaction is independent of immunoglobulins and coagulation factors will be performed under more critical conditions. Inhibitors of proteolytic enzymes and artificial substrates will be used to define the properties of the reaction. The role of phospholipids in the thromboplastin complex will be ascertained in relation to its effect on complement. Efforts will be directed to investigate whether other complement proteins are also thromboplastin substrates.